Correction to "On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review".

[This corrects the article DOI: 10.1021/acsptsci.1c00024.].

Enhancing Psychiatry Education through Podcasting: Learning from the Listener Experience.

OBJECTIVE: Podcasts have recently been introduced into psychiatry education, despite limited evidence evaluating podcasting in medical education. PsychEd is an educational, publicly available podcast targeting junior learners in psychiatry. This study characterized PsychEd's listeners and the podcast's role in their education. METHODS: The study involved a mixed-methods survey, followed by semi-structured phone interviews with respondents. There were 97 survey responders in total, of whom 9 participated in a telephone interview. Survey responses were coded as interval data and analyzed descriptively using statistical software. Interviews were transcribed and coded for emergent themes using a grounded theory model. RESULTS: PsychEd listeners represented an interprofessional audience, with 46 respondents (48%) being physicians or physicians in training, and 34 (35%) being allied mental health professionals. All respondents (100%) rated the podcast as "helpful" or "very helpful" for general knowledge. Listeners were attracted to PsychEd for the auditory learning format, the opportunity to review existing knowledge, the focus on core topics, the Canadian expertise, and the presentation of "clinical pearls." Respondents highlighted valuable qualities of a psychiatry podcast: conversational, case-based, narrative approach, longer episodes (i.e., 30-60 minutes) as compared to other medical specialties, and a clinical focus. Furthermore, they identified podcasts as an opportunity for shared interprofessional curricula. CONCLUSION: This study is the first to examine the motivations and experiences of listeners of a psychiatry educational podcast. The findings support existing literature on the benefits of podcasts in medical education. Future studies should explore the impact of podcasts on learning and behaviors.

Decreases in Suicidality Following Psychedelic Therapy: A Meta-Analysis of Individual Patient Data Across Clinical Trials.

Objective: Suicide is a global health concern, and innovative interventions that target suicidality are needed. While psychedelic therapy shows promise for a range of mental health concerns, including suicidality, not all psychedelic therapy trials have published their suicidality results and no meta-analysis has been published on the topic. Therefore, we completed the first meta-analysis of patient-level data on the effects of psychedelics on suicidality.Data Sources: We conducted a systematic search of MEDLINE, PsycINFO, and PubMed for all psychedelic therapy clinical trials (last search: November 5, 2020).Study Selection: We identified all psychedelic therapy trials that included a measure or measure-item that assesses suicidality.Data Extraction: Suicidality data were requested from study authors and extracted using a data extraction form developed for this study.Results: We identified 8, and successfully collected data from 7, relevant trials. Analysis of standardized mean differences (SMDs) indicated that, relative to baseline, psychedelic therapy was associated with large effect sizes for acute (80-240 min) and sustained (1 day, 1-8 weeks, and 3-4 months) decreases in suicidality (SMD range = -1.48 to -2.36; 95% CI range, -4.30 to 0.23). At 6 months, the effect size was medium (SMD = -0.65; 95% CI, -1.14 to -0.16). Reductions in suicidality were significant at all time points except for 7-8 weeks. Acute and post-acute elevations in suicidality were rare (6.5% and 3.0%, respectively).Conclusions: Limitations include heterogeneous samples and interventions, as well as limited sample size and number of studies. Results provide preliminary support for the safety of psychedelic therapy and its positive effect on suicidality. Controlled trials that specifically evaluate the effect of psychedelic therapy on suicidality may be warranted.

Management of adult tuberous sclerosis complex-related angiomyolipoma: A single-center experience.

INTRODUCTION: Tuberous sclerosis complex (TSC) is a rare, multi-system, genetic disease. A significant cause of TSC-related morbidity is potential bleeding from renal angiomyolipoma (AML). To pre-emptively decrease AML bleeding, mTOR inhibitors can be used; however, thresholds for initiating and maintaining everolimus therapy remain uncertain. Recent literature suggests not triggering active treatment of AMLs based on size thresholds alone. We evaluated the appropriateness of initiating everolimus therapy in asymptomatic patients after considering AML size, rate of growth, and other factors. METHODS: Diagnostic criteria developed by the 2012 International TSC Consensus Group and presence of AML were used as inclusion criteria. Medical and imaging reports of 11/20 TSC patients from a single center were reviewed. RESULTS: Mean age was 40.55 (±16.27) and 11 patients were female. Eight asymptomatic patients at high risk for complications underwent everolimus therapy, of which seven (88%) demonstrated decreased AML size, but multiple side effects were reported. Four high-risk asymptomatic patients did not undergo therapy due to side effect concerns, while four low-risk asymptomatic patients had stable AMLs under active surveillance. Four patients had reduced AMLs through local therapy. CONCLUSIONS: Everolimus treatment was effective for managing AML size in most high-risk, asymptomatic patients with tolerable side effects. AML size can remain relatively stable for asymptomatic, low-risk patients despite not receiving intervention(s). Patients with TSC-related AML can be safely managed with mTOR inhibitors like everolimus with shared decision-making, including factors such as bleeding risk, AML growth rate, and number and absolute size of AMLs.

On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review.

Use of classic psychedelics (e.g., psilocybin, ayahuasca, and lysergic acid diethylamide) is increasing, and psychedelic therapy is receiving growing attention as a novel mental health intervention. Suicidality remains a potential safety concern associated with classic psychedelics and is, concurrently, a mental health concern that psychedelic therapy may show promise in targeting. Accordingly, further understanding of the relationship between classic psychedelics and suicidality is needed. Therefore, we conducted a systematic review of the relationship between classic psychedelics (both non-clinical psychedelic use and psychedelic therapy) and suicidality. We identified a total of 64 articles, including 41 articles on the association between non-clinical classic psychedelic use and suicidality and 23 articles on the effects of psychedelic therapy on suicidality. Findings on the association between lifetime classic psychedelic use and suicidality were mixed, with studies finding positive, negative, and no significant association. A small number of reports of suicide and decreased suicidality following non-clinical classic psychedelic use were identified. Several cases of suicide in early psychedelic therapy were identified; however, it was unclear whether this was due to psychedelic therapy itself. In recent psychedelic therapy clinical trials, we found no reports of increased suicidality and preliminary evidence for acute and sustained decreases in suicidality following treatment. We identify some remaining questions and provide suggestions for future research on the association between classic psychedelics and suicidality.

Psychiatric Morbidity among Incarcerated Individuals in an Underserved Region of Nigeria: Revisiting the Unmet Mental Health Needs in Correction Services.

While epidemiological description of psychiatric morbidity can promote evidenceinformed mental health services, there is a paucity of such evidence among incarcerated individuals in prisons with underserved healthcare. We evaluated 250 incarcerated individuals detained in an underserved prison in north-western Nigeria with the Mini International Neuropsychiatric Inventory (MINI). Predominantly, study participants were men (97.6%) and the mean age was 35.4 (SD=13.5) years. The majority of the incarcerated individuals (81.2%) were awaiting trial, the most common crime was armed robbery (38.8%), and 16.4% of participants were recidivists. The prevalence of psychiatric morbidity was 47.4%, with major depression being the most common diagnosis (23.2%). The majority (92.8%) had no prior contact with psychiatric treatment. Being single, employed, and lacking prior psychiatric treatment were independently associated with psychiatric morbidity (R2=0.27). These findings underscore the need for better investment in correctional mental health services. Multi-pronged efforts with multisectoral collaboration between the government and other stakeholders to develop scalable interventions are advocated.

Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial.

RATIONALE: Suicidality is a major public health concern with limited treatment options. Accordingly, there is a need for innovative interventions for suicidality. Preliminary evidence indicates that treatment with the psychedelic ayahuasca may lead to decreases in depressive symptoms among individuals with major depressive disorder (MDD). However, there remains limited understanding of whether ayahuasca also leads to reductions in suicidality. OBJECTIVE: To examine the acute and post-acute effect of ayahuasca on suicidality among individuals with MDD. METHODS: We conducted a secondary analysis of an open-label trial in which individuals with recurrent MDD received a single dose of ayahuasca (N = 17). Suicidality was assessed at baseline; during the intervention; and 1, 7, 14, and 21 days after the intervention. RESULTS: Among individuals with suicidality at baseline (n = 15), there were significant acute (i.e., 40, 80, 140, and 180 min after administration) and post-acute (1, 7, 14, and 21 days after administration) decreases in suicidality following administration of ayahuasca. Post-acute effect sizes for decreases in suicidality were large (Hedges' g = 1.31-1.75), with the largest effect size 21 days after the intervention (g = 1.75). CONCLUSIONS: When administered in the appropriate context, ayahuasca may lead to rapid and sustained reductions in suicidality among individuals with MDD. Randomized, double-blind studies with larger sample sizes are needed to confirm this early finding.

Treatment Outcomes in Patients With Opioid Use Disorder Who Were First Introduced to Opioids by Prescription: A Systematic Review and Meta-Analysis.

OBJECTIVE: Prescription opioid misuse has led to a new cohort of opioid use disorder (OUD) patients who were introduced to opioids through a legitimate prescription. This change has caused a shift in the demographic profile of OUD patients from predominantly young men to middle age and older people. The management of OUD includes medication-assisted treatment (MAT), which produces varying rates of treatment response. In this study, we will examine whether the source of first opioid use has an effect on treatment outcomes in OUD. Using a systematic review of the literature, we will investigate the association between source of first opioid introduction and treatment outcomes defined as continuing illicit opioid use and poly-substance use while in MAT. METHODS: Medline, EMBASE, CINHAL, and PsycInfo were searched from inception to December 31st, 2019 inclusive using a comprehensive search strategy. Five pairs of reviewers conducted screening and data extraction independently in duplicate. The review is conducted and reported according to the PRISMA guidelines. A random-effects model was used for meta analyses assuming heterogeneity among the included studies. RESULTS: The initial search results in 27,345 articles that were screened, and five observational studies were included in the qualitative and quantitative analyses. Our results found that those who were introduced to opioids through a legitimate prescription were significantly less likely to have illicit opioid use (0.70, 95% CI 0.50, 0.99) while on MAT. They were also less likely to use cannabis (0.54, 95% CI 0.32, 0.89), alcohol (0.75, 95% CI 0.59, 0.95), cocaine (0.50, 95% CI 0.29, 0.85), and injection drug use (0.25, 95% CI 0.14, 0.43) than those introduced to opioids through recreational means. CONCLUSION: This study shows that the first exposure to opioids, whether through a prescription or recreationally, influences prognosis and treatment outcomes of opioid use disorder. Although the increased pattern of prescribing opioids may have led to increased OUD in a new cohort of patients, these patients are less likely to continue to use illicit drugs and have a different prognostic and clinical profile that requires a tailored approach to treatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017058143.

The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis.

BACKGROUND: Ketamine is established as a rapid and effective treatment in adults with treatment-resistant depression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes. METHODS: Effect size with respect to depression symptom reduction for each formulation and route of delivery was compared at discrete time-points (i.e., 24 h, 2-6 days, 7-20 days, 21-28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral routes of administration. Analysis was also conducted evaluating the effect size of racemic ketamine to esketamine. RESULTS: The pooled effect size for intranasal ketamine/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591-1.903, p < 0.01). At 2-6 days, the pooled effect size for intravenous ketamine/esketamine was g = 0.949 (n = 14, 95% CI: -0.308-2.206, p = 0.139). At 7-20 days, intranasal ketamine had a pooled effect size of g = 1.018 (n = 4, 95% CI: 0.499-1.538, p < 0.01). At 21-28 days, oral ketamine had a pooled effect size of g = 0.633 (n = 2, 95% CI: 0.368-0.898, p < 0.01). LIMITATIONS: Additional comparative studies are needed with regards to the efficacy of different formulations and routes of delivery. CONCLUSIONS: The short-term efficacy of intravenous and intranasal ketamine/esketamine for adults with TRD was established. Interpreting the efficacy of oral ketamine was limited by the need for studies with larger samples across independent sites. No conclusions regarding comparative efficacy of the disparate formulations and routes of delivery can be derived from this analysis. Direct comparative studies are needed to further inform treatment options for TRD.

A comparison of electronically-delivered and face to face cognitive behavioural therapies in depressive disorders: A systematic review and meta-analysis.

BACKGROUND: Cognitive behavioural therapy (CBT) is a widely used treatment for depression. However, limited resource availability poses several barriers to patients seeking access to care, including lengthy wait times and geographical limitations. This has prompted health care services to introduce electronically delivered CBT (eCBT) to facilitate access. Although previous reviews have compared the effects of eCBT to face-to-face CBT, there is an overall lack of adequately powered and up-to-date evidence in the literature to provide a reliable comparison between the two modes of administration. The purpose of this study is to evaluate the effects of eCBT compared to face-to-face CBT through a systematic review of the literature. METHODS: To be eligible for this review, studies needed to be randomized controlled trials evaluating the clinical effectiveness of any form of eCBT compared to face-to-face CBT. These encompassed studies evaluating a wide range of outcomes including severity of symptoms, adverse outcomes, clinically relevant outcomes, global functionality, participant satisfaction, quality of life, and affordability. There were no restrictions on participant age or sex.We searched MEDLINE, EMBASE, Psych Info, Cochrane CENTRAL and CINAHL databases from inception to February 20th, 2020 using a comprehensive search strategy. All stages of literature screening and data extraction were completed independently in duplicate. Data extraction and risk of bias analyses, including GRADE ratings, were conducted on studies meeting inclusion criteria. Qualitative measures are reported in a narrative summary. We pooled quantitative data in meta-analyses to provide an estimated summary effect. This review adheres to PRISMA reporting guidelines. FINDINGS: In total, we included 17 studies in our analyses. Our results demonstrated that eCBT was more effective than face-to-face CBT at reducing depression symptom severity (Standardized mean difference [SMD]: -1.73; 95% confidence interval [CI]: -2.72, -0.74; GRADE: moderate quality of evidence). There were no significant differences between the two interventions on participant satisfaction (SMD 0.13 95%; CI -0.32, 0.59; GRADE: low quality of evidence). One RCT reported eCBT to be less costly than face-to-face CBT (GRADE: low quality of evidence). Results did not differ when stratified by subgroups such as participant age and study location. INTERPRETATION: Although we found eCBT to have moderate evidence of effectiveness in reducing symptoms of depression, high heterogeneity among studies precludes definitive conclusions for all outcomes. With the current reliance and accessibility of technology to increasing number of people worldwide, serious consideration in utilizing technology should be given to maximize accessibility for depression treatments. Our results found eCBT is at least as effective as face to face CBT, thus eCBT should be offered if preferred by patients and therapists. FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Adverse Outcomes Associated with Prescription Opioids for Acute Low Back Pain: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute low back pain (ALBP) is a common clinical complaint that can last anywhere from 24 hours to 12 weeks. In recent years, there has been an opioid epidemic which is linked to the increased availability of prescription opioids. Though guidelines recommend that in the treatment of ALBP, opioids should be used when other treatments fail, we have seen an increase in opioid prescriptions for ALBP. With this crisis, it is important to examine if there are any adverse outcomes associated with prescribing opioids for ALBP. OBJECTIVE: We aim to review the published literature to examine the adverse outcomes associated with opioid use for ALBP. STUDY DESIGN: We performed a systematic review with meta-analysis in accordance with our published protocol and PRISMA guidelines. SETTING: The review was conducted at McMaster University. METHODS: Various electronic databases for articles published from inception to September 30, 2017, inclusive. Both randomized clinical trials and observational studies on the impact of opioid use in ALBP in the adult population were included. Eight pairs of independent reviewers performed screening, data extraction, and assessment of methodological quality. The identified articles were assessed for risk of bias using sensitivity analysis. Trials with comparative outcomes were reported in a meta-analysis using a fixed effects model. RESULTS: A total of 13,889 studies were initially screened for the review and a total of 4 studies were included in the full review, of which 2 studies were meta-analyzed. Our results showed that prescribing opioids for ALBP was significantly associated with long-term continued opioid use (1.57, 95% CI, 1.06-2.33). There was no significant association found between unemployment duration and prescribing opioids for ALBP (3.54, 95% CI, -7.57 to 14.66). LIMITATIONS: Due to the limited number of studies that considered unemployment, only an unpooled analysis was conducted. Among the included studies there was both statistical and clinical heterogeneity due to differences in methodology, study design, risk of selection or performance bias. Most of the studies had an unclear or high risk of bias and poorly defined side effects. CONCLUSIONS: Due to the lack of literature examining long-term adverse outcomes associated with prescribing opioids for ALBP, no definitive conclusions can be made. However, with the literature available, there does seem to be risk associated with prescribing opioids for ALBP so there is a great need to conduct further investigations examining these adverse outcomes for ALBP patients. KEY WORDS: Acute low back pain, opioids, prescriptions, low back pain, long-term use, opioid use disorder.

Harmonization of United States, European Union and Canadian First-in-Human Regulatory Requirements for Radiopharmaceuticals-Is This Possible?

In recent years, several new radiotracers and radionuclide therapies have been developed. There is a renaissance in nuclear medicine and molecular imaging today, for example, in terms of the ability to image and treat neuroendocrine and prostate malignancies. In order to be able to bring a new drug product from bench to bedside and assist patients, while also ensuring patient safety, stringent regulations must be met. However, differences in regulatory requirements, often based on jurisdictional politics rather than scientific evidence, can hinder global co-operation, increase expense, and slow progress. In an effort to rise above these differences, nuclear medicine advocacy organizations, regulators, and international agencies have begun to identify commonalities in the regulations to achieve harmonization. Indeed, a more streamlined approach to radiopharmaceutical drug development across jurisdictions could be achieved through establishing harmonized requirements for pre-clinical studies and manufacturing standards. This paper provides an educational overview of the regulatory and submission requirements governing investigational radiopharmaceuticals for first-in-human radiopharmaceuticals across the European and North American continents. It is hoped that through ongoing collaboration, regulatory reform and harmonization can become a reality and speed access to the most up-to-date evidence-based patient care for all.